758   Low Lymph Node Viral Load Despite High Viremia in Seroconverters Supports Early HAART Intervention.

K. Tenner-Racz¹, L. Perrin², H. J. Stellbrink³, M. Youle⁴, D. Hawkins⁴, D. Cooper⁵, S. Staszewski⁶, C. Tsoukas⁷, D. Sereni⁸, P. M. Girard⁹, A. Lazzarin¹⁰, G. Tambussi¹¹, P. Vernazza¹¹, R. Weber¹², K. Stuttard¹³, J. M. Vauthier¹³, C. Python¹³, L. Goh¹³, and P. Racz¹.
¹Bernhard-Nocht Inst., Hamburg, Germany;²Univ. of Geneva, Geneva, Switzerland;³Univ. Eppendorf, Hamburg, Germany;⁴Dept. of Infectious Diseases, London, UK;⁵Natl. Ctr. in HIV, Epidemiology and Clinical Res., Sydney, Australia;⁶Klin. der J. W. Goethe Univ., Frankfurt, Germany;⁷Montreal Gen. Hosp., Montreal, Quebec, Canada;⁸Hosp. St. Louis;⁹Hosp. Rothschild, Paris, France;¹⁰Ospedale San Raffaele, Milan, Italy;¹¹St. Gallen Kantonsspital;¹²Univ. Zurich, Zurich, Switzerland;¹³and Glaxo Wellcome, London, UK.

Background:An understanding of the pathogenesis of primary HIV-1-infection (PHI) provides a rationale for early initiation of HAART. Since lymph nodes (LN) are the main site of HIV-1 replication and storage, we compared the expression of virologic and immunologic markers in the LN of recent seroconverters (mean 1 Western blot band; n = 14) from the QUEST PHI study versus untreated asymptomatic chronically infected (CI) patients enrolled in the Hamburg/Geneva cohorts (n = 13).

Methods:In situ hybridization for HIV-1 RNA, immunohistochemistry, quantitation of cell-associated unspliced messenger and genomic RNA (mRNA) and DNA (cDNA).

Results:Plasma viremia was higher in patients with PHI versus CI. Mean viremia (range) log₁₀c/mL: 5.39 (4.55-6.16) in PHI vs. 4.32 (<2.7-5.48). In contrast, LN sections contained less HIV RNA⁺cells/mm²in PHI than in CI (1.48 vs. 3.42, p = 0.0098, Mann-Whitney). Similarly, cDNA and mRNA were significantly lower in PHI than in CI: DNA log c/10⁶LNMC: 3.31 in PHI vs. 4.06 in CI, p < 0.001; mRNA log c/10⁶LNMC: 4.52 in PHI vs., 5.62 in CI, p < 0.001, t-test. Extensive virus trapping by follicular dendritic cells (FDC) was present in CI but minimal or absent in PHI. On average, 22.8%(CI) versus 9.4% (PHI) of the germinal center area was occupied by dense (CI) and delicate (PHI) deposits of FDC-bound RNA. In both groups >95% of RNA⁺cells were CD4⁺T cells and, respectively, 43% and 60% of these did not express activation markers (Ki-67, CD25) and were positive for p27^Kip1; a negative regulator of the cell cycle (a cyclin-dependent kinase inhibitor); indicating that most infected cells were nonreplicating CD4 T-cells.

Conclusion:Difference in viremia and viral trapping between PHI and CI is likely to be reflective of low viral clearance linked to the concentration and/or quality of anti-HIV antibodies at time of seroconversion. The unexpectedly low levels of HIV-infected cells and replication in LN of PHI patients suggest that early HAART might reduce viral spreading and thus influence long-term viral replication.